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This cross-sectional study aimed to investigate the associations between salivary testosterone concentrations and cognitive function in 70-year-old Japanese elderly people without dementia and stroke.Participants were 197 Japanese community-dwelling people aged 69-71 years. Their salivary samples were collected, and their cognitive function was assessed using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Participants were also administered a 10-item recall and a 24-item recognition test. The data for 179 (106 men and 73 women) individuals were analyzed, excluding individuals with a past history of stroke and dementia. Multivariate logistic regression analyses were performed after adjusting for lifestyle factors and analyzing data separately for men and women.MoCA-J scores showed that men with low testosterone concentrations had a significantly greater risk of low cognitive performance than those with high testosterone concentrations (adjusted odds ratio: 4.72, 95% confidence interval: 1.06-21.00), while no significant association was found in women. The 10-item recall test scores showed that higher testosterone concentrations were significantly associated with greater recall in the second trial in women (standardized beta = 0.24, P = 0.040), whereas no significant association was found in men. Salivary testosterone concentrations were positively associated with better cognitive performance in older men and women.The associations between salivary testosterone concentrations and cognitive function were shown by different tasks for men and women. Geriatr Gerontol Int 2022; 22: 1040-1046.

The G allele of FOXO3 gene (single-nucleotide polymorphism; rs2802292) is strongly associated with human longevity. However, knowledge of the effect of FOXO3 in older populations, men or women, with heart disease is limited. This cross-sectional study in Japan included 1836 older adults in the 70- and 80-year-old groups. DNA samples isolated from buffy coat samples of peripheral blood were used to genotype FOXO3 (rs2802292). Self-reports were used to obtain heart disease data according to physician diagnosis. Multiple logistic regression was used to test the association by adjusting for the traditional risk factor of heart disease. The prevalence of heart disease in women FOXO3 G-allele carriers was higher than noncarriers (16.7% vs 11.6%, p = .022). The prevalence of coronary heart disease was lower for FOXO3 G carriers in the 70-year-old group for both sexes (men: 9.3% vs 4.3%, p = .042 and women: 10% vs 9%, p = .079, respectively). The G allele was negatively associated with heart disease after adjusting for diabetes, hypertension, dyslipidemia, and smoking in men (odds ratio [OR] = 0.70, 95% confidence intervals [CIs], 0.49–0.99, p = .046), although the association was weaker after full adjustment. In contrast, women carriers of the FOXO3 G allele showed a positive association with heart disease after total adjustment (OR = 1.49, 95% CI, 1.00–2.21, p = .049). In conclusion, the longevity-associated G allele of FOXO3 was observed to have contrasting associations with heart disease prevalence according to sex in older Japanese. To further confirm this association, a longitudinal study and a large sample size will be required.

High-quality diets and regular physical activity (PA) are considered healthy behaviors (HBs). HBs are associated with many health outcomes and are expected to improve quality of life. Although implementing HBs is important, the relationship between dietary patterns (DPs) and PA has not been well investigated, especially among those aged ≥ 85. This study used data from the Tokyo Oldest Old survey on Total Health study to examine the relationship between DPs and PA in a cross-sectional study. The dietary survey used the brief self-administered diet history questionnaire to estimate the intake of 58 foods. After energy adjustment, principal component analysis was performed to identify major DPs. A validated questionnaire was used to evaluate PA, and linear regression analysis was used to investigate the association between DPs and PA, considering confounders. A total of 519 participants were included. Three major DPs (‘Various plant foods’, ‘Fish and mushrooms’, ‘Cooked rice and miso soup’) were identified. ‘Various plant foods’ was similar to DPs previously named ‘Healthy’ or ‘Prudent’, and its trend was positively associated with higher PA. This study observed the implementation of HBs even among those aged ≥ 85, suggesting that a trend toward a healthier diet is associated with higher PA.

Background Very few studies have examined the relationship of oral health with physical functioning and frailty in the oldest old (> 85 years). We examined the association of poor oral health with markers of disability, physical function and frailty in studies of oldest old in England and Japan. Methods The Newcastle 85+ Study in England (n = 853) and the Tokyo Oldest Old Survey on Total Health (TOOTH; n = 542) comprise random samples of people aged > 85 years. Oral health markers included tooth loss, dryness of mouth, difficulty swallowing and difficulty eating due to dental problems. Physical functioning was based on grip strength and gait speed; disability was assessed as mobility limitations. Frailty was ascertained using the Fried frailty phenotype. Cross-sectional analyses were undertaken using logistic regression. Results In the Newcastle 85+ Study, dry mouth symptoms, difficulty swallowing, difficulty eating, and tooth loss were associated with increased risks of mobility limitations after adjustment for sex, socioeconomic position, behavioural factors and co-morbidities [odds ratios (95%CIs) were 1.76 (1.26–2.46); 2.52 (1.56–4.08); 2.89 (1.52–5.50); 2.59 (1.44–4.65) respectively]. Similar results were observed for slow gait speed. Difficulty eating was associated with weak grip strength and frailty on full adjustment. In the TOOTH Study, difficulty eating was associated with increased risks of frailty, mobility limitations and slow gait speed; and complete tooth loss was associated with increased risk of frailty. Conclusion Different markers of poor oral health are independently associated with worse physical functioning and frailty in the oldest old age groups. Research to understand the underlying pathways is needed.

Type 2 Diabetes (T2D) is an emerging public health problem in Asia. Although ethnic specific mtDNA polymorphisms have been shown to contribute to T2D risk, the functional effects of the mtDNA polymorphisms and the therapeutic potential of mitochondrial-derived peptides at the mtDNA polymorphisms are underexplored. Here, we showed an Asian-specific mitochondrial DNA variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c, an insulin sensitizing mitochondrial-derived peptide. Meta-analysis of three cohorts (n = 27,527, J-MICC, MEC, and TMM) show that males but not females with the C-allele exhibit a higher prevalence of T2D. In J-MICC, only males with the C-allele in the lowest tertile of physical activity increased their prevalence of T2D, demonstrating a kinesio-genomic interaction. High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice. Like the human data, female mice were unaffected. Mechanistically, K14Q-MOTS-c leads to diminished insulin-sensitization in vitro. Thus, the m.1382A>C polymorphism is associated with susceptibility to T2D in men, possibly interacting with exercise, and contributing to the risk of T2D in sedentary males by reducing the activity of MOTS-c.

Aim The association between serum uric acid (UA) and atherosclerosis in old people is controversial. Therefore, in this study, we clarified this association by assessing serum UA and common carotid atherosclerosis examined by carotid ultrasound in community-dwelling older people in their 70s, 80s and 90s in the SONIC study. Methods A cross-sectional study was conducted involving 538 men and 577 women recruited from the community. The analysis was performed using serum UA as the explanatory variable and the maximum carotid intima-media thickness (max-CIMT) and mean-IMT as the dependent variables. The analysis was performed by multiple regression using traditional risk factors for atherosclerosis as adjustment variables. Results Analysis of the association between serum UA and IMT revealed a significant correlation only in women >70 years old. Max-CIMT (β = 0.081, 95% CI = 0.026, 0.136; P = 0.004) and mean-IMT (β = 0.015, 95% CI = 0.003, 0.029; P = 0.016) were significant. In the analysis of each age group, a significant correlation was only found in women in their 70s for mean-IMT (β = 0.031, 95% CI = 0.008, 0.053; P = 0.008). Conclusion In community-dwelling women aged about 70 years old, elevated serum UA may be an independent risk factor for IMT thickening as a surrogate marker for atherosclerosis. Geriatr Gerontol Int 2020; ••: ••-••.

BACKGROUND A variant of c.14429G>A (p.Arg4810Lys, rs112735431) in the ring finger protein 213 gene (RNF213; NM_001256071.2) has been recently identified as a risk allele for pulmonary arterial hypertension (PAH). PAH can be added as a new member of RNF213-associated vascular diseases, which include Moyamoya disease and peripheral pulmonary stenosis. Our aim was to identify the clinical features and outcomes of PAH patients with this variant. METHODS Whole-exome sequencing was performed in 139 idiopathic (or possibly heritable) PAH patients. RESULTS The RNF213 p.Arg4810Lys variant was identified in a heterozygous state in 11 patients (7.9%). Time-course changes in hemodynamics after combination therapy in the patients with the RNF213 p.Arg4810Lys variant were significantly poorer compared with those carrying the bone morphogenic protein receptor type 2 (BMPR2) mutation (n = 36) (comparison of changes in mean pulmonary arterial pressure, p = 0.007). The event-free rate of death or lung transplantation was significantly poorer in RNF213 p.Arg4810Lys variant carriers than in BMPR2 mutation carriers (5-year event-free rate since the introduction of prostaglandin I2 infusion, 0% vs 93%, respectively; p CONCLUSIONS Idiopathic PAH patients with the RNF213 p.Arg4810Lys variant are associated with poor clinical outcomes even in recent times. Earlier consideration of lung transplantation might be required for RNF213 p.Arg4810Lys variant carriers who are developing PAH. Documentation of the RNF213 p.Arg4810Lys variant, as well as already known pathogenic genes, such as BMPR2, can provide clinically relevant information for therapeutic strategies, leading to a personalized approach for the treatment of PAH.

BackgroundThe oldest old, defined as those aged 90 or over, is now the fastest-growing population sector. This study aimed to determine reference values for several physical performance measures (PPMs) among 90-year-olds using internationally standardized measurements and to clarify the characteristics of these indices by comparing their results for 90-year-olds with those for older people 70 and 80.MethodsWe used the Septuagenarians, Octogenarians, and Nonagenarians Investigation with Centenarians (SONIC) study data from 2010 to 2018. The study subjects were 70, 80, and 90-year-olds in the target area eligible to participate in the venue. Excluding those certified for long-term care, the final number of eligible persons is 70s cohort 1000 (2010), 80s cohort 973 (2011), and 90s cohort 690. 90s cohort only consisted of three survey waves: 2012, 2015, and 2018. We used hand grip strength and score on the Short Physical Performance Battery (SPPB) for our physical performance measurements. In addition, we statistically analyzed sex and age differences.ResultThe simple mean ± standard deviation (SD) for the 90-year-old respondents were in men, 24.1 ± 5.4 kg in hand grip strength, 0.80 ± 0.22 m/s in usual gait speed, 17.2 ± 6.73 s in 5times chair stand, 5.89 ± 4.42 s in tandem balance, and 8.3 ± 2.2 in SPPB respectively and in women, 14.4 ± 4.0 kg in hand grip strength, 0.72 ± 0.20 m/s in usual gait speed, 17.8 ± 7.89 s in 5times chair stand, 4.72 ± 4.35 s in tandem balance, and 7.5 ± 2.4 in SPPB, respectively. For all PPMs, the age 90 cohort was statistically significantly different from the age 70 and 80 cohorts (all trendsP ConclusionsOur study yielded inclusive sex-specific reference values and appraisal standards for major physical performance measures not certified as requiring long-term care, community-dwelling, oldest old Japanese. The characteristics of age-related decline in physical performance differed between the upper and lower extremity assessments.

Background The relationship between moderate alcohol drinking or other alcohol drinking patterns such as frequency, beverage type, and situation of drinking and cognitive function is not sufficiently clear in older people. The purpose of this study was to investigate the association between alcohol drinking patterns and cognitive function in community-dwelling Japanese people aged 75 and over. Methods This study was a cross-sectional design based on a prospective cohort study called the SONIC study. Subjects were older people aged 75-77 or 85-87 who voluntarily participated in 2016-2017. Drinking information was collected for daily drinking frequency, daily drinking intake, beverage type, and non-daily drinking opportunity. Cognitive function was measured using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Other potential confounding factors evaluated were age, sex, medical factors, and psychosocial factors. An analysis of covariance was performed to evaluate the MoCA-J score relative to drinking frequency or alcohol intake. Multiple regression analysis was performed to investigate the association between beverage type or non-daily drinking opportunity and the MoCA-J score. Results The final number of participants analyzed was 1,226. The MoCA-J score for participants who reported drinking alcohol 1–6 days/week was significantly higher than that for those who reported drinking none or every day. No significant difference in the MoCA-J score was observed relative to daily alcohol intake. In terms of beverage type, wine was associated positively with the MoCA-J score. Non-daily drinking opportunity was also associated positively with the MoCA-J score. Conclusions Moderate-frequency drinking, wine consumption, and non-daily drinking opportunities were associated with higher cognitive function in community-dwelling Japanese aged 75 and over. Further longitudinal studies are needed to clarify the causal relationships.

ObjectiveThis study aimed to identify associations between multimorbidity and subjective health outcomes among the very old persons, after adjusting for coexisting conditions such as frailty and depression.Study setting and participantsThis was an observational cross-sectional study involving 1012 independent, community-dwelling very old persons (507 men, 505 women; aged 85–89 years) in Kawasaki city, Japan.Outcome measuresThe primary outcome was the cross-sectional associations between multimorbidity and poor self-rated health (SRH) and life satisfaction using binary logistic regression. The secondary outcome was the association of subjective health with each chronic condition.ResultsThe prevalence of multimorbidity (≥2 conditions) was 94.7%, and the average number of chronic conditions was 4.47±1.9. Multimorbidity was significantly associated with poor SRH in the adjusted model only when six or more chronic conditions were present (OR 4.80; 95% CI 1.34 to 17.11; p=0.016). Cerebrovascular disease, heart disease, respiratory disease, connective tissue disease and arthritis showed significant associations with poor SRH after multivariate adjustment. Sex-specific analysis replicated associations between multimorbidity with six or more conditions and SRH in both men and women, while the diseases with the greatest impact on SRH differed between men and women. Most conditions were not associated with low satisfaction with life scale, with the exception of arthritis (OR 1.92, 95% CI 1.32 to 2.78, p=0.001).ConclusionsMultimorbidity is prevalent in the independent, community-dwelling very old persons and is associated with poor SRH when six or more conditions are present; conditions causing mobility limitations, such as cerebrovascular disease, connective tissue disease and arthritis, have a negative impact on SRH.Trial registration numberUMIN000026053.

The aim of this study was to clarify the association between dietary protein intake and decline in the estimated glomerular filtration rate (eGFR) among Japanese older adults.We used the data of the Septuagenarians, Octogenarians and Nonagenarians Investigation with Centenarians (SONIC) study, an ongoing narrow-age range cohort study: 69-71 years, 79-81 years and 89-91 years. The outcome variable, change in eGFR, was estimated from serum creatinine measured at the baseline and 3-year follow up, and the exposure variable, protein intake, was calculated using the brief-type self-administered diet history questionnaire at the baseline. Associations between eGFR change and protein intake were determined by multiple linear regression analysis.The mean eGFR change per year was -1.89 mL/min/1.73 mProtein intake among community-dwelling older adults was not associated with lower eGFR, and for older chronic kidney disease patients, protein and animal protein intakes were more beneficial in maintaining eGFR. The results provide evidence that protein intake should not be restricted for older patients with chronic kidney disease, including the very elderly. Geriatr Gerontol Int 2022; 22: 286-291.

Background and objectives Nutritional deficiencies, renal impairment and chronic inflammation are commonly mentioned determinants of anaemia. The aim of this study was to investigate the effects of these determinants, singly and in combination, on anaemia in the very old. Method The TULIPS Consortium consists of four population-based studies in oldest-old individuals: Leiden 85-plus Study, LiLACS NZ, Newcastle 85+ study, and TOOTH. Five selected determinants (iron, vitamin B12, and folate deficiency; low estimated glomerular filtration rate (eGFR); and high C-reactive protein (CRP)) were summed. This sum score was used to investigate the association with the presence and onset of anaemia (WHO definition). The individual study results were pooled using random-effects models. Results In the 2216 participants (59% female, 30% anaemia) at baseline, iron deficiency, low eGFR and high CRP were individually associated with the presence of anaemia. Low eGFR and high CRP were individually associated with the onset of anaemia. In the cross-sectional analyses, an increase per additional determinant (adjusted OR 2.10 (95% CI 1.85–2.38)) and a combination of ≥2 determinants (OR 3.44 (95% CI 2.70–4.38)) were associated with the presence of anaemia. In the prospective analyses, an increase per additional determinant (adjusted HR 1.46 (95% CI 1.24–1.71)) and the presence of ≥2 determinants (HR 1.95 (95% CI 1.40–2.71)) were associated with the onset of anaemia. Conclusion Very old adults with a combination of determinants of anaemia have a higher risk of having, and of developing, anaemia. Further research is recommended to explore causality and clinical relevance.

Background Polypharmacy is a serious concern among older adults and is frequently related to adverse outcomes, including health problems, reduced quality of life, and increased medical expenses. Although personality traits are associated with health behaviors and diseases, the effect of polypharmacy on personality traits is unclear. Therefore, we examined the association of personality traits with polypharmacy among community-dwelling older adults. Methods This cross-sectional study analysed data on 836 community-dwelling older adults aged 69–71 years who participated in the Japanese longitudinal cohort study of Septuagenarians, Octogenarians, and Nonagenarians Investigation with Centenarians. Polypharmacy was defined as the intake of ≥ 5 medications concurrently. Personality traits were assessed using the Japanese version of the NEO-Five-Factor Inventory (NEO-FFI). A five-factor model of personality traits, including “neuroticism,” “extraversion,” “openness,” “agreeableness,” and “conscientiousness,” was measured by the NEO-FFI. Results The average number of medications was about 3 in both men and women. Among the participants, polypharmacy was observed in 23.9% of men and 28.0% of women. Multivariable logistic regression analysis showed that neuroticism (adjusted odds ratio [aOR] per 1 point increase = 1.078, 95% confidence interval [CI] = 1.015–1.144) in men and extraversion (aOR = 0.932, 95% CI = 0.884–0.983) in women were associated with polypharmacy. Conclusions Higher neuroticism in men and lower extraversion in women were associated with polypharmacy. This study suggests that personality traits may be involved in the process leading to the development of polypharmacy. Information on individual personality traits may help medical professionals in decision-making regarding medication management for lifestyle-related diseases.

Background Chronic and lifestyle-related diseases and social status were reported to be associated with long-term care (LTC). The social factors should be treated as social sub-groups of which characteristics show social profiles. However, few previous studies considered that. The present study aimed to investigate the associations between LTC and chronic and lifestyle-related diseases, and whether the associations were modified by the social sub-groups in the community-dwelling elderly. Method A cross-sectional study was conducted among 1004 community-dwelling participants aged 80 and 90. LTC was used as the outcome. Chronic and lifestyle-related diseases (i.e., stroke, heart disease, joint pain, osteoporosis, lung disease, cancer, hypertension, dyslipidemia, and diabetes) were used as the predictors. Education, household income, residential area, and support environment were analyzed by latent class analysis (LCA) to derive social profiles. We obtained odds ratios (ORs) of LTC from those diseases and tested interactions between those diseases and the social profiles by logistic regression analyses. Result The participants were categorized into two sub-groups of social factors (n = 675 and 329) by LCA. Logistic regression analyses showed ORs (95% CI) of LTC were 4.69 (2.49, 8.71) from stroke, 2.22 (1.46, 3.38) from joint pain, 1.99 (1.22, 3.25) from osteoporosis, and 2.05 (1.22, 3.40) from cancer adjusting for the social sub-groups. There were no significant interactions between the social subgroups and those diseases in relation to LTC except for osteoporosis. Conclusion The associations between LTC and chronic and lifestyle-related diseases were significant with adjusting for the social sub-groups, and not modified by that except osteoporosis.

Aim Few cohort studies targeting the oldest-old individuals have been carried out. The subiculum in the hippocampus is thought to be related to memory function, and atrophy of this structure might result in the conversion from amnestic mild cognitive impairment to Alzheimer's disease. Thus, we sought to examine the relationship between subiculum volumes and memory function in individuals aged ≥95 years, using a novel cognitive examination called the Addenbrooke's Cognitive Examination III (ACE-III) and an advanced magnetic resonance imaging analytical method, Multiple Automatically Generated Templates Brain Segmentation Algorithm (MAGeTbrain), to measure hippocampal subfield volumes. Methods A part of the cohort data of the Arakawa 95+ study for the oldest-old aged ≥95 years was used. A total of 10 individuals completed all of the examinations. The MAGeT brain was applied to estimate the subfield volumes of the hippocampus. Correlation analyses and multiple regression analyses were carried out to examine a relationship among ACE-III memory scores and the subfield volumes in the hippocampus, including the subiculum. Results There was a significant relationship between ACE-III memory scores and subdivision volumes. Regression analyses showed that subiculum volumes were associated with ACE-III memory scores in the oldest-old individuals (β = 0.721, P = 0.019; F1, 8 = 8.67, adjusted R2 = 0.46). Conclusions The subiculum might play a pivotal role in memory function in the oldest-old individuals aged ≥95 years. The present finding warrants further research including larger sample sizes. Geriatr Gerontol Int 2019; 19: 347-351.

Objectives:Centenarians have survived into very late life, but whether they reach very old age in good health remains unclear. The purpose of this study was to compare the cardiovascular health status and cognitive functioning of centenarians in the United States with centenarians in Japan.Design, Setting, and Participants:This cross-national design compared centenarians from the United States and Japan. The sample of U.S. centenarians was recruited from the Georgia Centenarian Study and included 287 centenarians. The sample of Japanese centenarians was recruited from the Tokyo Centenarian Study and included 304 centenarians.Measurements:Cognitive functioning was assessed with a mental status questionnaire, and cardiovascular disease by a health history assessment, blood pressure, and selected blood parameters.Results:The results suggest that Tokyo centenarians had lower disease experiences and BMI values, when compared to Georgia centenarians, but blood pressure was higher among Japanese centenarians. Lower levels of hemoglobin in Japanese centenarians and higher levels of C-reactive protein in Georgia were also found. The positive association of hypertension and albumin levels with cognitive functioning and the negative association of stroke occurrence with cognitive functioning were replicated in both countries. Differential effects were obtained for heart problems, BMI, and C-reactive protein (with positive effects for Tokyo centenarians, except for C-reactive protein).Conclusion:For extremely old individuals, some markers of cardiovascular disease are replicable across countries, whereas differential effects for cardiovascular health also need to be considered in cardiovascular health.

Background There is increasing evidence of causal links between poor mastication and cognitive impairment, but possible effects of dietary hardness, which clearly affects mastication, on cognitive function are unknown. Objective We investigated the hypothesis that hardness of the habitual diet would be associated with cognitive function among older Japanese adults. Methods The subjects of this cross-sectional study were 635 Japanese community-dwelling people aged 69-71 years. The masticatory muscle activity required for the habitual diet was used to determine dietary hardness. Consumption of 38 foods was assessed by a validated, brief-type, self-administered diet history questionnaire. A published database was then used to estimate the masticatory muscle activity involved in the ingestion of these foods. The Japanese version of the Montreal Cognitive Assessment (MoCA-J) was used for the measurement of cognitive function. Results The principal contributors to dietary hardness were cooked rice (28.0%), green leafy vegetables (5.1%), dried fish (4.9%), and pork and beef (4.6%). There was a positive association between dietary hardness and MoCA-J score that was robust to adjustment for potential confounders (MoCA-J score per 100-unit increase in dietary hardness: β = 0.83 [95% CI: 0.08, 1.59], P = 0.03). These results did not change materially even after exclusion of subjects who reported substantial changes in their diet for any reason (β = 0.94 [95% CI: 0.02, 1.86], P = 0.04). Conclusion This preliminary cross-sectional study suggests that dietary hardness might have a beneficial effect on cognitive function in older Japanese people. Further prospective studies with more accurate measurements are needed to confirm this finding.

Purpose Oral stereognostic ability (OSA) is a useful indicator of oral perception to recognize food characteristics during mastication. Previous studies have shown associations between dietary intake and oral health status, such as taste perception. However, the effect of oral sensory ability on dietary intake is unclear. The purpose of this study was to investigate the association between oral sensory ability and dietary intake in older Japanese complete denture wearers. Methods This cross-sectional study included 164 participants aged 69–71 or 79–81 years old, wearing both maxillary and mandibular complete dentures. OSA test was used to evaluate oral tactile perception. Diet during the preceding month was assessed using a self-administered diet history questionnaire. Multivariable linear regression analysis was conducted to assess the association between OSA score and food and nutrient intake after adjusting for age, sex, socioeconomic factors, and occlusal force. Results The bivariate analysis showed that OSA score was significantly and positively correlated with intake of green and yellow vegetables and negatively correlated with intake of cereals among examined foods. OSA score was also positively correlated with intake of vitamins A, B2, and C and α-tocopherol (as a substitute for vitamin E) among examined nutrients. After adjusting for age, sex, socioeconomic factors, and occlusal force, OSA score remained significantly associated with intake of green and yellow vegetables and α-tocopherol. Conclusions OSA was significantly associated with intake of green and yellow vegetables in older complete denture wearers.

The Japanese government has implemented a new screening program to promote measures to avoid worsening lifestyle-related diseases and frailty among the older population. In this effort, the government formulated a new health assessment questionnaire for the screening program of old-old adults aged ≥75 years. The questionnaire comprises 15 items, of which 12 address frailty, two address general health status, and one addresses smoking habits. This study examined the construct validity of this questionnaire, using the explanatory factor analysis (EFA) and confirmatory factor analysis (CFA). The data used in this study were drawn from a mail-in survey conducted in 2020 as part of the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study. A total of 1576 respondents (range, 78–99 years of age) were included in the study. Although the EFA did not show an interpretable factor structure of the questionnaire with 15 items, the CFA using only 12 frailty-related items showed the goodness of fit for a higher-order factor “frailty”, and the five frailty-related sub-factors model was acceptable. These results suggest that the total score of the 12 frailty-related items in the questionnaire can be used as an indicator of the degree of “frailty”.

Background On April 7, 2020, Japan declared a state of emergency due to the first wave of coronavirus disease 2019 (COVID-19) with the associated social distancing likely to have had a great impact on older adults’ lifestyle and health. This study aimed to explore the behavioral changes and personal hygiene practices in relation with background psychosocial and health characteristics of older adults during the COVID-19 emergency. Methods A cross-sectional telephonic survey was conducted with the participants of the Kawasaki Aging and Wellbeing Project (KAWP), an on-going longitudinal cohort study of older adults aged 85 or older. The interviews were conducted using a structured questionnaire consisting of 11 closed questions regarding behavioral changes and personal hygiene practices during the state of emergency. Sociodemographic and health data were obtained from the KAWP baseline survey conducted 2.2 years before the telephonic survey. Results Overall, 487 participants from the KAWP responded to the telephonic survey (response rate: 89.2%). 94.5% of the respondents reported no changes in basic lifestyle habits, such as eating, sleeping, smoking, and drinking, whereas 28.1% reported a decrease in physical activity, and 54.6% reported going out less frequently. One-third of the respondents reported a decrease in the number of people to converse with, as well as the amount of time to converse. For personal hygiene practices, 93.8% reported wearing a mask when they went out, and 50.3% reported an increased frequency of handwashing. Multiple logistic regression analysis revealed that engagement in physical activity at baseline (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.23–3.08), smartphone ownership (OR = 2.15, 95% CI = 1.33–3.47), and visual impairment (OR = 1.79; 95% CI = 1.10–2.91) were independently associated with decreased physical activity during the COVID-19 emergency. Female respondents and smartphone ownership were significantly associated with more frequent handwashing. Conclusions The study revealed that older adults in an urban setting responded to the COVID-19 emergency with behavioral changes. The findings of this study have implications for the design of preventive strategies to maintain the health and wellbeing of at-risk older adults.

Background and objective Physical activity (PA) confers protection to individuals from the risk of death. However, in the very old, the dose-response relationship between PA and all-cause mortality and the possible biological mediators of this association are less known. We investigated whether PA predicts 6-year all-cause mortality and what biomarkers mediate the association. Design Prospective cohort data from the Tokyo Oldest Old Survey on Total Health study. Setting Community-dwelling population. Participants A total of 441 women and men aged over 85 years. Measurements Questionnaire-based PA was assessed at baseline and 3-year and 6-year follow-up visits. Survival status was confirmed up to the 6-year follow-up visit (153 deaths, 34.7%). Data of plasma albumin, cholinesterase, NT-proBNP, interleukin-6, cystatin C, and HbA1c levels were collected. For mediation analysis for survival analysis, we used the baseline PA and biomarkers with Weibull distribution accelerated failure time model and linear regression model adjusted for age, sex, body mass index, smoking, education level, and Mini-Mental State Examination. Results A curvilinear relationship was observed in the association between baseline PA and all-cause mortality. Compared to the inactive (0 METs*h/week), light amount of PA was associated with a lower risk of mortality. Compared to the highest tertile of PA (11.2 METs*h/week), higher PA did not reduce the risk of death. Circulation levels of albumin and cholinesterase mediated the association between baseline PA and all-cause mortality (proportion mediated, 54%, both; p Conclusions Compared to completely inactive, light PA reduces the risk of all-cause mortality in the very old population. Mediation analysis suggests that protein synthesis in the liver may mediate the association between PA and all-cause mortality. Further studies are needed to understand the underlying association between PA, nutrition, and death.

Superoxide dismutase 3 (SOD3), an antioxidant enzyme, is known as extracellular SOD (EC-SOD) because it is the predominant form in extracellular fluids. The diversity of plasma EC-SOD concentration is associated with the SOD3 p.R231G missense variant genotype. To clarify the association among SOD3 genotype, plasma EC-SOD concentration, and comorbidity in Oldest Old, we analyzed genome-wide associations with plasma EC-SOD concentration and associations between EC-SOD concentration and medical history classified by the SOD3 genotype in the Very Old (85–99 years old, n = 505) and Centenarians (over 100 years old, n = 595). The results revealed that SOD3 p.R231G was the most significant variant associated with plasma EC-SOD concentration. Although no significant difference was observed in medical histories between the SOD3 p.R231G variant non-carriers and carriers, higher EC-SOD concentration in plasma of SOD3 p.R231G variant non-carriers was associated with a high odds ratio for chronic kidney disease (OR = 2.70, 95% CI = 1.98–3.72) and low odds ratio for diabetes mellitus (DM) (OR = 0.61, 95% CI = 0.39–0.95). Comparison with 11 plasma biomarkers for age-related disease showed that plasma EC-SOD concentration correlated with adiponectin and estimated glomerular filtration rate with creatinine correction; therefore, we deduced that EC-SOD co-operates with adiponectin and possesses beneficial functions for DM in the Oldest Old.

Centenarians have a decreased susceptibility to ageing-associated illnesses, chronic inflammation and infectious diseases

Background: Physical function is a strong predictor of the adverse outcomes of cardiovascular disease in older populations. However, studies of healthy older people on the prevention of coronary heart disease (CHD) are very limited. Objectives: We prospectively examined the association of walking speed and handgrip strength with CHD in the community-dwelling older populations. Methods: The study cohort in Japan included 1272 older people free from heart disease at the baseline. Physical function was identified based on walking speed and handgrip strength assessment at the survey site. Any new case of CHD was identified based on a self-reported doctor's diagnosis. Cox-proportion hazard models were adjusted for covariate factors to examine the CHD risk. Results: During the 7-year follow-up, 45 new cases of CHD (25 men and 20 women) were documented. Slow walking speed was strongly associated with CHD risk after adjusting for all confounding factors in the total participants and women (hazard ratio (HR)= 2.53, 95%confidence interval (CI), 1.20-5.33, p=0.015, and HR= 4.78, 95% CI,1.07-21.35, p=0.040, respectively), but not in men. Weak grip strength was associated with CHD after age-adjustment (HR= 2.45, 95%CI, 1.03-5.81, p=0.043) only in men. However, after additional multivariate adjustment, the associations were getting weaker.

Background: Subclinical and overt thyroid dysfunction is easily detectable, often modifiable, and, in younger age groups, has been associated with clinically relevant outcomes. Robust associations in very old persons, however, are currently lacking. This study aimed to investigate the associations between (sub-)clinical thyroid dysfunction and disability in daily living, cognitive function, depressive symptoms, physical function, and mortality in people aged 80 years and older. Methods: Four prospective cohorts participating in the Towards Understanding Longitudinal International older People Studies (TULIPS) consortium were included. We performed a two-step individual participant data meta-analysis on source data from community-dwelling participants aged 80 years and older from the Netherlands, New Zealand, United Kingdom, and Japan. Outcome measures included disability in daily living (disability in activities of daily living [ADL] questionnaires), cognitive function (Mini-Mental State Examination [MMSE]), depressive symptoms (Geriatric Depression Scale [GDS]), physical function (grip strength) at baseline and after 5 years of follow-up, and all-cause five-year mortality. Results: Of the total 2116 participants at baseline (mean age 87 years, range 80-109 years), 105 participants (5.0%) were overtly hypothyroid, 136 (6.4%) subclinically hypothyroid, 1811 (85.6%) euthyroid, 60 (2.8%) subclinically hyperthyroid, and 4 (0.2%) overtly hyperthyroid. Participants with thyroid dysfunction at baseline had nonsignificantly different ADL scores compared with euthyroid participants at baseline and had similar MMSE scores, GDS scores, and grip strength. There was no difference in the change of any of these functional measures in participants with thyroid dysfunction during five years of follow-up. Compared with the euthyroid participants, no 5-year survival differences were identified in participants with overt hypothyroidism (hazard ratio [HR] 1.0, 95% confidence interval [CI 0.6-1.6]), subclinical hypothyroidism (HR 0.9 [CI 0.7-1.2]), subclinical hyperthyroidism (HR 1.1 [CI 0.8-1.7]), and overt hyperthyroidism (HR 1.5 [CI 0.4-5.9]). Results did not differ after excluding participants using thyroid-influencing medication. Conclusions: In community-dwelling people aged 80 years and older, (sub-)clinical thyroid dysfunction was not associated with functional outcomes or mortality and may therefore be of limited clinical significance.

Background Preventing the need for long-term care (LTC) by identifying physical function risk factors are important to decrease the LTC burden. The objective of this study was to investigate whether grip strength and/or walking speed, which are components of the frailty definition, are associated with LTC in community-dwelling older and oldest people. Methods The participants were 1098 community-dwelling older and oldest people who had not received LTC at the baseline. The endpoint was receiving LTC after the baseline survey. The independent variables were grip strength and walking speed, and participants were divided into two groups based on these variables. The confounding factors were age, sex, the Japanese version of the Montreal Cognitive Assessment (MoCA-J), hypertension, diabetes mellitus, stroke, joint diseases, living alone, body mass index, and serum albumin. We calculated the hazard ratio of receiving LTC using the Cox proportional hazard model. Results Among the 1098 participants, 107 (9.7%) newly received LTC during the follow-up. Regarding the physical function, only slow walking speed was significantly correlated with LTC after adjusting for all confounding factors except the MoCA-J score (HR = 1.74, 95% CI = 1.10–2.75, P = .018). However, slow walking speed was still a risk factor for LTC after adjusting for the MoCA-J score and other confounding factors (HR = 1.64, 95% CI = 1.03–2.60, P = .037). Conclusions The findings from this study may contribute to a better understanding of slow walking speed as a factor related to LTC, which might be a criterion for disability prevention and could serve as an outcome measure for physical function in older people.

Supercentenarians (those aged ≥110 years) are approaching the current human longevity limit by preventing or surviving major illness. Identifying specific biomarkers conducive to exceptional survival might provide insights into counter-regulatory mechanisms against aging-related disease. Here, we report associations between cardiovascular disease-related biomarkers and survival to the highest ages using a unique dataset of 1,427 oldest individuals from three longitudinal cohort studies, including 36 supercentenarians, 572 semi-supercentenarians (105–109 years), 288 centenarians (100–104 years), and 531 very old people (85–99 years). During follow-up, 1,000 participants (70.1%) died. Overall, N-terminal pro-B-type natriuretic peptide (NT-proBNP), interleukin-6, cystatin C and cholinesterase are associated with all-cause mortality independent of traditional cardiovascular risk factors and plasma albumin. Of these, low NT-proBNP levels are statistically associated with a survival advantage to supercentenarian age. Only low albumin is associated with high mortality across age groups. These findings expand our knowledge on the biology of human longevity., Supercentenarians are approaching the current longevity limit by avoiding or surviving major illness, thus identifying biomarkers for exceptional survival might provide insights into the protection against disease of aging. Here, the authors show low NT-proBNP and high albumin in plasma are the biological correlates of survival to the highest ages.

Periodontal disease and arteriosclerotic disease are greatly affected by aging. In this study, the association of conventional risk factors and periodontal disease with atherosclerosis was longitudinally examined in Japanese older adults. Subjects in this study were 490 community-dwelling septuagenarians (69-71 years) randomly recruited from the Basic Resident Registry of urban or rural areas in Japan. At the baseline examination, all subjects underwent socioeconomic and medical interviews; medical examinations, including examinations for carotid atherosclerosis, hypertension, diabetes mellitus, and dyslipidemia; and conventional dental examinations, including a tooth count and measurement of probing pocket depth (PPD). After 3 years, 182 septuagenarians who had no atherosclerosis at the baseline examination were registered and received the same examination as at the baseline. In the re-examination conducted 3 years after the baseline survey, 131 (72.0%) of the 182 participants who had no atherosclerosis at the baseline examination were diagnosed with carotid atherosclerosis. Adjusting and analyzing the mutual relationships of the conventional risk factors for atherosclerosis by multiple logistic regression analysis for the 171 septuagenarians with a full set of data, the proportion of teeth with PPD ≥ 4 mm was independently related to the prevalence of atherosclerosis (odds ratio: 1.029, P 0.022). This longitudinal study of Japanese older adults suggests that periodontal disease is associated with the onset/progression of atherosclerosis. Maintaining a healthy periodontal condition may be an important factor in preventing the development and progression of atherosclerosis.

We investigated the association of systolic blood pressure (SBP) level with physical frailty and cognitive function in community-dwelling older Japanese. Using the 'Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians' survey as the baseline, we performed a cross-sectional analysis of people aged 70 ± 1 (n = 1000), 80 ± 1 (n = 978), and 90 ± 1 (n = 272) years. Medical histories and medications were collected via interviews conducted by medical professionals. Blood pressure (BP), grip strength, gait speed, and cognitive function were examined on site. Trend analysis and multiple regression analysis were used to determine the association of the SBP level with physical frailty and cognitive function. The principal finding was that the association of SBP with physical frailty and cognitive function varied depending on characteristics such as age, physical and cognitive function, and antihypertensive medication use. A lower SBP level was associated with a higher prevalence of physical frailty only among 80-year-olds who were on antihypertensive medication. A significant association was found between higher SBP and lower cognitive function among 70-year-olds, while among 90-year-olds, the opposite was found. No association was found among participants who were 80 years old or among participants of all ages without antihypertensive medication. Our finding that an inverted association between SBP and geriatric syndrome exists suggests that the treatment of older patients must be individualized to prevent geriatric syndrome.

ObjectivesTo measure the use of healthcare services and assistive devices by centenarians in five countries.DesignCross-sectional study using a survey questionnaire.SettingCommunity-dwelling and institutionalised centenarians living in Japan, France, Switzerland, Sweden and Denmark.Participants1253 participants aged 100 or in their 100th year of life, of whom 1004 (80.1%) were female and 596 (47.6%) lived in institutions.Main outcome measuresRecent use of medical visits, nursing care at home, home-delivered meals, acute care hospital stays overnight, professional assessments such as sight tests, mobility aids and other assistive devices. A set of national healthcare system indicators was collected to help interpret differences between countries.ResultsThere was considerable variability in the healthcare services and assistive devices used by centenarians depending on their country and whether they were community-dwelling or institutionalised. In contrast to the relatively homogeneous rates of hospitalisation in the past year (around 20%), community-dwelling centenarians reported widely ranging rates of medical visits in the past 3 months (at least one visit, from 32.2% in Japan to 86.6% in France). The proportion of community-dwellers using a mobility device to get around indoors (either a walking aid or a wheelchair) ranged from 48.3% in Japan to 79.2% in Sweden. Participants living in institutions and reporting the use of a mobility device ranged from 78.6% in Japan to 98.2% in Denmark.ConclusionsOur findings suggest major differences in care received by centenarians across countries. Some may result from the characteristics of national healthcare systems, especially types of healthcare insurance coverage and the amounts of specific resources available. However, unexplored factors also seem to be at stake and may be partly related to personal health and cultural differences.

Supercentenarians, people who have reached 110 years of age, represent an ultimate model of human longevity. We have conducted research from both biomedical and psychosocial perspectives to clarify the factors that contribute to healthy longevity. The current study described the clinical course of the oldest lived man in the world.Kimura Jiroemon, who is the verified oldest man in recorded history, lived for more than 116 years. We conducted a longitudinal investigation including physical and psychological assessments, blood data, and electrocardiogram (ECG) from the age of 111 and obtained medical data such as computed tomography (CT) images during the course of hospitalizations in the last year of his life.At the age of 111, Jiroemon was almost independent regarding activities of daily living. Additionally, his Philadelphia Geriatric Center Morale Scale score was 15/17, indicating high psychological well-being. His biological data included first-degree atrioventricular (AV) block on ECG; mild decreases of hemoglobin (11.6 g/dL), hematocrit (36.2%), and albumin levels (3.5 g/dL); and elevated serum cystatin C levels (1.32 mg/L), indicating potential dysfunction of the renal and electrical conduction systems. He then lived without fatal illness until the age of 115 years. At this age, he lost consciousness, and his ECG revealed complete AV block. At the first hospitalization for intensive examination, his doctor recommended implanting a cardiac pacemaker, but he and his family declined. On December 12, 2012, his condition rapidly worsened, and he was hospitalized twice for heart failure because of AV block. On May 11, 2013, he lost consciousness after breakfast, and he was hospitalized for the fourth time. He was diagnosed with pneumonia and heart failure based on his chest CT findings and elevated brain natriuretic peptide levels (160 pg/mL), and died on June 12, 2013 at the age of 116.Despite having no cardiovascular risk factors throughout his life, Jiroemon developed heart failure from potential heart and kidney dysfunction, suggesting that aging of the cardiorenal system was the ultimate pathology of the oldest man in the world. His clinical course represents a model of both suppression of morbidity and extreme longevity. Comprehensive health and longevity research studies from physical and psychological aspects are required.

Objectives The purpose of our cross-sectional study was to investigate the relationship between gerotranscendence and oral health-related quality of life (OHR-QOL). To our knowledge, this is the first study to investigate the relationship between gerotranscendence and OHR-QOL. Methods Participants (total n = 1969; 70-year-old group, n = 999; 80-year-old group, n = 970) were drawn from resident lists in four areas of Japan: one urban area and one rural area in each of two geographical regions. OHR-QOL was measured using the Geriatric Oral Health Assessment Index (GOHAI). Measurement of occlusal force was performed using pressure-sensitive sheets. Gerotranscendence was assessed with the Japanese Gerotranscendence Scale Revised (JGS-R). We used multiple linear regression analysis to examine the relationships among OHR-QOL and other variables. Results Geriatric Oral Health Assessment Index score was significantly correlated with occlusal force, number of teeth, financial status and JGS-R score on linear regression analysis. Conclusion Degree of gerotranscendence was significantly and independently correlated with degree of OHR-QOL in our sample.

Oral tactile perception is important for better mastication, appetite, and enjoyment of food. However, previous investigations have not utilized comprehensible variables thought to have negative effect on oral perception, including aging, denture wearing, and cognitive function. The aim of this study was to elucidate the impact of cognitive function on oral perception in independently living older individuals. The study sample was comprised of 987 participants (466 males, 521 females; age 69–71 years). Oral examinations, assessments of cognitive function in preclinical level by Montreal Cognitive Assessment (MoCA)-J, and determination of oral stereognostic ability as an indicator of oral perception were performed. Related variables were selected by univariate analyses; then, multivariate logistic regression model analysis was conducted. Univariate analyses revealed that number of teeth, removable dentures usage, and cognitive function respectively had a significant relationship with stereognostic score. Next, the subjects were classified into good and poor perception groups (lowest 17.4%) according to oral stereognostic ability. Logistic regression analysis revealed that lower cognitive function was significantly associated with poor oral perception (OR = 0.934, p = 0.017) after controlling for other variables. Cognitive decline even in preclinical stage was associated with reduced oral perception after controlling for gender, tooth number and denture use in independent living older people. This study suggested that preclinical level of change in cognitive function affected oral perception. Dental practitioners and caregivers may need to pay attention to reduced oral perception among older people even if they do not have trouble in daily life.

Identifying the correct length of life for long-lived individuals is highly important for the social and natural sciences, as well as for policymaking. The purposes of this paper are to propose a standardized age verification procedure and to report on the age verification case of Jiroemon Kimura (J.K.), who is assumed to be the longest lived man in the world. We propose two verification processes that we have named face validity and concurrent validity of age verification. We collected official documents, and non-official records to check face validity. We also gathered life episodes told by J.K. and historical records to evaluate concurrent validity. Although we found several date inconsistencies among documents and mismatches between told episodes and actual dates of events, no critical discordances were discovered. In conclusion, we could verify that J.K. was born on April 19, 1897 and passed away on June 12, 2013 at the age of 116years and 54days.

The scope and purpose of this review was to summarize the aims, methods, findings, and future of centenarian and (semi)-supercentenarian studies in Japan, particularly those from our own interdisciplinary laboratory. Medically, approximately 97% of centenarians contract chronic diseases including hypertension and gastrointestinal disease; however, they present with few cardiovascular risk factors. The low prevalence of diabetes mellitus and carotid atherosclerotic plaques is peculiarities of centenarians, which could be associated with high adiponectin levels. While conducting the Tokyo centenarian study (TCS), we found that only 20% of centenarians enjoyed physical and cognitive independence at the age of 100 years, although most remained independent in daily living until into their 90s. Those who maintained physical independence at 100 years of age were highly likely to become semi-supercentenarians (over 105 years) or even supercentenarians (beyond 110 years). We also describe parts of results of the Japan Semi-supercentenarian Study (JSS), which showed that the suppression of chronic inflammation is an important driver of successful aging at extreme old age. Telomere maintenance and an extremely low frequency of APOE-ε4 alleles are genetic peculiarities of (semi)-supercentenarians. The available data confirm our conviction that semi-supercentenarians are a more appropriate model for the study of human longevity.

This study investigated the relationships between muscle echo intensity (EI), physical activity (PA), and functional mobility in 108 Japanese (88–92 years). We measured EI and muscle thickness (MT) at the midpoint of the anterior superior iliac spine and patella using B-mode ultrasound. Light and moderate-to-vigorous PA (LPA and MVPA) were assessed with a triaxial accelerometer. The timed up and go (TUG) test was used to measure for functional mobility. EI, but not MT, was significantly associated with both TUG scores (β = 0.17, p = .047) and MVPA (β = –0.31, p = .01) when adjusted by potential confounders. However, association between EI and TUG disappeared after adjusted for MVPA. Meanwhile, MVPA was significantly associated with TUG scores independent of EI (β = –0.35, p < .001). Although EI of anterior thigh muscles might be a weaker predictor of functional morbidity than MVPA, it is a noninvasive and practical approach for assessing muscle quality in the very old.

Objective The aim of this study was to clarify whether perceived swallowing problems affect the life expectancy of very elderly individuals. Background In an ageing society, oral function affects health status. In particular, a decline in swallowing function may increase the risk of various diseases, morbidity and malnutrition. Materials and Methods We evaluated 526 elderly individuals aged ≥85 years. All participants completed a questionnaire and underwent oral, physical and mental health examinations. The comprehensive oral health assessment comprised a face-to-face interview that included a questionnaire on swallowing function. We estimated hazard ratios and 95% confidence intervals using the Cox proportional hazards model, adjusting for potential confounders between perceived swallowing problems and all-cause mortality over a 3-year period. Results Over a 3-year follow-up period, 88 of 526 participants died and 68 participants complained of perceived swallowing problems. Perceived swallowing problems had statistically significant associations with physical status and function and nutrition. In the univariate analysis, perceived swallowing problems had statistically significant associations with an approximately 1.9-fold higher risk of all-cause mortality during the 3-year period (HR: 1.89, 95% CI: 1.14-3.14). In the multivariate analysis, the statistically significant association between perceived swallowing problems and all-cause mortality remained after adjusting for various confounding factors (HR: 1.73, 95% CI: 1.03-2.92). Conclusion Perceived swallowing disorders should be verified by a clinical examination, as they are associated with other health outcomes and increased all-cause mortality.

Age-related deterioration in physical and oral health reduces healthy life expectancy and is thus an important problem for very elderly people. We investigated the effects of satisfaction with dietary life (SDL) in everyday life on oral health-related quality of life (OHRQoL) and subjective well-being and examined associations between these factors. We evaluated 426 elders aged 85 years or older. All participants completed a questionnaire that inquired about age, gender, drinking status, body mass index, cognitive function, disability, and comorbidities, among other covariates. Oral, physical, and mental health conditions were also examined. Associations of questionnaire results for SDL with items on subjective well-being (Philadelphia Geriatric Center Morale Scale [PGC] and World Health Organization-5 [WHO-5]) and OHRQoL (Geriatric Oral Health Assessment Index [GOHAI]) were confirmed with multiple logistic regression analysis. In a multivariate model adjusted for various confounders, participants with self-reported "enjoyable" SDL had significantly lower risks for having the lowest scores on the GOHAI, PGC, and WHO-5 (odds ratio [OR] = 0.460, 95% confidence interval [CI] = 0.277-0.762; OR = 0.589, 95% CI = 0.348-0.996; and OR = 0.452, 95% CI = 0.263-0.775, respectively). These associations remained after further adjustment for number of teeth.

Aim To assess the burdens of polypharmacy and the drug burden index in community-dwelling elder people. Methods The survey was conducted on 396 participants who participated in The Kawasaki Wellbeing Project from March to December 2017. We investigated the associations between the drug burden and the physical/cognitive/mental outcomes. The drug burden was determined by calculating the number of medications and the drug burden index (DBI) based on the use of anticholinergic and sedative drugs. A multivariate regression analysis was conducted for the outcome measures ADL, IADL, MMSE, J-CHS, and EQ5D5L after adjusting for the sex, age, number of diseases, education level, smoking history, and alcohol history. Results A total of 389 subjects were analyzed, the mean age of the population was 86 years old, and 187 people (48%) were male. Polypharmacy was reported in 243 people (62%), and DBI exposure was reported for 142 people (36.5%). We found that this population was physically healthy, with a median ADL of 100, and had high quality of life, with a median EQ5D5L of 0.895. Polypharmacy was found to be related to the J-CHS (β: 0.04) and EQ5D5L (-0.01). The DBI was also related to the EQ5D5L (-0.04). Conclusion These results showed that even though this population was healthier than the general Japanese elderly population, the drug burden of polypharmacy and high dosages of anticholinergic/sedative drugs exerted significant negative effects on frailty and the quality of life. Additional research should be conducted to investigate the long-term effects of polypharmacy and anticholinergic/sedative drugs on elderly people.

Due to the recent rapid increase in the number of elderly people in the world, health management and maintenance in elderly people have become important issues. Centenaria, who are older than 100 years, tend to stay independent in their daily life with maintenance of cognitive function until the later stage of their life compared with elderly people who die earlier. In this review, we summarize the characteristics of centenarians, the genetic risk and protective factors for longevity, and intersections between research on centenarians and dementia research.

Background Cognitive impairment is a major health concern among older and oldest people. Moreover, stroke is a relevant contributor for cognitive decline and development of dementia. The study of cognitive decline focused on stroke as the important risk factor by recruiting older and oldest is still lagging behind. Therefore, the aim of this study was to investigate the importance of stroke as a risk factor of cognitive decline during 3 years in community dwelling older and oldest people. Methods This study was longitudinal study with a 3-year follow-up in Japan. The participants were 1333 community dwelling older and oldest people (70 years old = 675, 80 years old = 589, and 90 years old = 69). Data collected included basic data (age, sex, and history of stroke), vascular risk factors (hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, and current smoking), and social factors (educational level, frequency of going outdoors, long-term care (LTC) service used, and residential area). The Japanese version of the Montreal Cognitive Assessment (MoCA-J) was decline of ≥2 points was defined as cognitive decline. Multiple logistic regression analysis was used to investigate the association between stroke and other risk factors with cognitive decline during a 3-year follow-up. Results The fit of the hypothesized model by multiple logistic regression showed that a history of stroke, advanced age, and greater MoCA-J score at the baseline were important risk factors, while the presence of dyslipidemia and a higher educational level were protective factors that were significantly correlated with cognitive decline during the 3-year follow-up. Conclusions The cognitive decline after the 3-year follow-up was influenced by the history of stroke and advanced age, while greater MoCA-J score at the baseline was positively associated with subsequent 3 years cognitive decline. The protective factors were the presence of dyslipidemia and a higher educational level. Therefore, these factors are considered important and should be taken into consideration when searching for creative solutions to prevent cognitive decline after stroke in community dwelling older and oldest people.

OBJECTIVES Many older people lose their teeth. However, few studies have examined whether the number of remaining teeth or the amount of occlusal support is more important for tooth loss that occurs in older age after adjusting for systemic factors. The purpose of this study was to investigate comprehensively the factors related to tooth loss over a period of 6 years, including occlusal support in 70- and 80-year-old community-dwelling Japanese people. METHODS This cohort study included 296 participants in the 70-year-old group and 232 in the 80-year-old group. The number of teeth of all participants was recorded at baseline and after 6 years, and the participants were divided into two groups according to the number of teeth lost (0 or 4 or more). Occlusal support was classified into three groups based on posterior occlusal support. Mean probing pocket depth, tooth brushing habits, frequency of dental check-ups, education level, economic status and systemic factors (carotid atherosclerosis, hypertension, diabetes mellitus, dyslipidemia, cognitive function and smoking habits) were evaluated. Multiple logistic regression analysis was performed to investigate the relationship of tooth loss with occlusal support and systemic factors. RESULTS Logistic regression analysis revealed that mean probing pocket depth (odds ratio [OR] = 5.70, 95% confidence interval [CI] = 2.70-12.04, P

Although high blood pressure (BP) and BP variability have been reported to be associated with cognitive impairment, few studies have investigated the association between home BP (HBP) and cognitive function in the oldest-old. The aim of this study was to evaluate whether the value of and the day-to-day variability in HBP was associated with cognitive function in a Japanese community-dwelling oldest-old population. Among 111 participants aged 85-87 years, cognitive function was assessed using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). HBP was measured two times every morning for a median of 30 days. The value of and variability in HBP were calculated as the average and coefficient of variation (CV) of the measurements, respectively. The associations of HBP variability with MoCA-J were examined using multiple linear regression models. Of 111 participants, 47.7% were men, and 64.0% were taking medications for hypertension. The mean HBP was 141.9 ± 14.8/72.2 ± 8.4 mmHg, and the mean CV of HBP was 6.7 ± 1.9/6.8 ± 2.4. The mean total MoCA-J score was 22.9 ± 3.5. The MoCA-J score was significantly lower with increasing CVs of both systolic BP (b = -0.36, p = 0.034) and diastolic BP (b = -0.26, p = 0.046) after adjustment for possible confounding factors. The value of HBP was not associated with MoCA-J. In the community-dwelling oldest-old population, higher day-to-day HBP variability, but not the value of HBP, was associated with cognitive impairment. When measuring HBP, attention should be paid not only to the values but also to their variations.

Background Instrumental Activities of Daily Living (IADL) is an indicator of whether a community-dwelling elderly can live independently. IADL decline was reported to be associated with aging and depression. The present study aimed to investigate whether the association between IADL decline and depressive symptoms differs with aging, using two age groups of community-dwelling Japanese elderly in their 70s and 80s. Methods We conducted longitudinal analysis among participants in their 70s and 80s at the baseline from Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians (SONIC) study. IADL was assessed by The Tokyo Metropolitan Institute of Gerontology (TMIG) index of competence. As a main predictor, depressive symptoms were measured by the five-item version of the Geriatrics Depression Scale (GDS-5). As possible confounders, we considered cognitive function, body mass index, solitary living, education, economic status, medical history of stroke and heart disease, hypertension, dyslipidemia, diabetes, and sex. We obtained odds ratios (ORs) of IADL decline for having depressive symptoms in each age group (70s/80s) and tested interactions between depressive symptoms and age groups in relation to IADL decline in 3 years by logistic regression. Additionally, to confirm age group differences, we conducted multiple group analysis. Results There were 559 participants in their 70s and 519 in their 80s. Compared to participants without depressive symptoms, those with depressive symptoms had higher OR of IADL decline in 70s (OR [95% CI] = 2.33 [1.13, 4.78]), but not in 80s (OR [95% CI] = 0.85 [0.46, 1.53]). There were significant interactions between depressive symptoms and age groups in relation to IADL decline (p-value = 0.03). Multiple group analyses showed differences between the age groups by Akaike information criterion (AIC), and ORs (95%CI) decline for depressive symptoms was 2.33 (1.14, 4.77) in 70s and 0.85 (0.47, 1.54) in 80s. Conclusion The association of depressive symptoms and IADL decline during the 3 years was significantly different between the 70s and 80s age groups, and significant association was found only in people in their 70s. Detecting depressive symptoms may be a key for preventing IADL decline in people in their 70s and not for those in their 80s.

The apolipoprotein E4 (APOE ε4) allele has attracted attention as an age-related genetic factor, both in neurology and gerontology. To understand the effects of the APOE ε4 allele on mortality in elderly individuals, we combined Japanese prospective cohort studies comprising 535 very old individuals (85–99 years of age) and 930 centenarians (over 100 years of age) and analyzed the association between mortality rates and candidate factors, including the APOE ε4 allele. APOE genotyping revealed an inverse correlation between the APOE ε4 allele carrier rate and age. Additionally, APOE ε4 allele carrier rate in centenarian men was significantly lower than that in centenarian women. The association analysis between APOE ε4 allele carriers and all-cause mortality indicated that APOE ε4 carriers showed significantly higher mortality rates than the APOE ε4 noncarriers among men in the very old group. Further analysis using Cox proportional hazard models indicated that cause-specific mortalities, including pneumonia and severe dementia, were associated with APOE ε4 carriers. These findings indicate that the APOE ε4 allele shows phenotypic male-specific adverse effects in the very old, which would explain the high mortality rate observed in this group, resulting in a low APOE ε4 allele carrier rate in centenarian men.

Aim The objective of this study was to clarify the relationship between cognitive function and the serum albumin/globulin ratio (A/G ratio) in community-dwelling Japanese older adults. Methods Randomly extracted residents in both urban and rural parts of Japan were enrolled in this study. A total of 1827 participants with a mean age of 70 or 80 years were recruited. A venue survey method was carried out with comprehensive studies, including interviews, blood collection, physical examination and cognitive function tests. Results Univariate analysis showed a significant positive correlation between the total Japanese version of the Montreal Cognitive Assessment score and the serum A/G ratio at the age of 70 and 80 years, in which better cognitive function was associated with a high serum A/G ratio. Multiple regression analysis with the total Japanese version of the Montreal Cognitive Assessment score as the dependent variable showed that the serum albumin level, serum globulin level, serum A/G ratio, C-reactive protein, years of formal education and sex were related to the Japanese version of the Montreal Cognitive Assessment total score at the age of 70 years, and that the serum albumin level, serum globulin level, serum A/G ratio, C-reactive protein, years of formal education and stroke were related at the age of 80 years. The serum A/G ratio showed a better correlation than the serum globulin levels at the age of 70 and 80 years (70 years: β = 0.131 vs -0.111, 80 years: β = 0.108 vs -0.071). Conclusions We found a correlation between cognitive function and the serum A/G ratio in community-dwelling older people, suggesting that nutritional status and chronic inflammation might influence cognitive function. Geriatr Gerontol Int 2019; 19: 967-971.

Significance Exceptionally long-lived people such as supercentenarians tend to spend their entire lives in good health, implying that their immune system remains active to protect against infections and tumors. However, their immunological condition has been largely unexplored. We profiled thousands of circulating immune cells from supercentenarians at single-cell resolution and identified CD4 T cells that have cytotoxic features. This characteristic is very unique to supercentenarians, because generally CD4 T cells have helper, but not cytotoxic, functions under physiological conditions. We further profiled their T cell receptors and revealed that the cytotoxic CD4 T cells were accumulated through clonal expansion. The conversion of helper CD4 T cells to a cytotoxic variety might be an adaptation to the late stage of aging., Supercentenarians, people who have reached 110 y of age, are a great model of healthy aging. Their characteristics of delayed onset of age-related diseases and compression of morbidity imply that their immune system remains functional. Here we performed single-cell transcriptome analysis of 61,202 peripheral blood mononuclear cells (PBMCs), derived from 7 supercentenarians and 5 younger controls. We identified a marked increase of cytotoxic CD4 T cells (CD4 cytotoxic T lymphocytes [CTLs]) as a signature of supercentenarians. Furthermore, single-cell T cell receptor sequencing of 2 supercentenarians revealed that CD4 CTLs had accumulated through massive clonal expansion, with the most frequent clonotypes accounting for 15 to 35% of the entire CD4 T cell population. The CD4 CTLs exhibited substantial heterogeneity in their degree of cytotoxicity as well as a nearly identical transcriptome to that of CD8 CTLs. This indicates that CD4 CTLs utilize the transcriptional program of the CD8 lineage while retaining CD4 expression. Indeed, CD4 CTLs extracted from supercentenarians produced IFN-γ and TNF-α upon ex vivo stimulation. Our study reveals that supercentenarians have unique characteristics in their circulating lymphocytes, which may represent an essential adaptation to achieve exceptional longevity by sustaining immune responses to infections and diseases.

Human influenza A(H2N2) viruses emerged in 1957 and were replaced by A(H3N2) viruses in 1968. The antigenicity of human H2N2 viruses has been tested by using ferret antisera or mouse and human monoclonal antibodies. Here, we examined the antigenicity of human H2N2 viruses by using human plasma samples obtained from 50 aged individuals who were born between 1928 and 1933 and from 33 younger adult individuals who were born after 1962. The aged individuals possessed higher neutralization titers against H2N2 viruses isolated in 1957 and 1963 than those against H2N2 viruses isolated in 1968, whereas the younger adults who were born between 1962 and 1968 possessed higher neutralization titers against H2N2 viruses isolated in 1963 than those against other H2N2 viruses. Antigenic cartography revealed the antigenic changes that occurred in human H2N2 viruses during circulation in humans for 11 years, as detected by ferret antisera. These results show that even though aged individuals were likely exposed to more recent H2N2 viruses that are antigenically distinct from the earlier H2N2 viruses, they did not possess high neutralizing antibody titers to the more recent viruses, suggesting immunological imprinting of these individuals with the first H2N2 viruses they encountered and that this immunological imprinting lasts for over 50 years.